Using 12 different and elaborate broth, agar and cell culture procedures, we failed to isolate either mycoplasmas, ureaplasmas, spiroplasmas or chlamydiae from the synovial fluids of ten rheumatoid arthritis {RA} and six non-rheumatoid arthritis {NRA} patients. In addition, 35 RA and 12 NRA sera were also examined. Although some of the sera had moderately high metabolism inhibition antibody titers to some of the ten human Mycoplasma species, especially M. pneumoniae, a ommon respiratory pathogen, and to some of the eight U. urealyticum serovars, especially serovars V and VII, there were no significant differences in the two patient groups to these agents. Five RA patients had serum titers of 1:32 and eight had titers of 1:16 to M. pneumoniae and two patients had higher titers in their synovial fluids {1:16} than in sera {1:4}. Two RA patients had moderately high serum titers of 1:32 and 1:128 to U. urealyticum serovar V and ten RA patients had relatively high titers of from 1:32 to 1:512 to serovar VII. The GMT titer to serovar V in synovial fluids of RA patients was higher, but not quite significantly different from that of NRA patients {p.0.056]. However, RA patients had low, but significantly higher GMT titers to Spiroplasma mirum, SMCA, a mycoplasma isolated from a rabbit tick, in both their serum {p.0.016} and synovial fluids {p.0.023} than did NRA patients, but the nature of the inhibition was not determined. Reports on the possible role of infectious agents in the pathogeneses of rheumatoid arthritis are reviewed.